Set1 RRM domain

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Cartoon representation and surface properties of RRM1. (a) Stereoscopic view of the _-sheet facing the RNP motifs. RNP2 and RNP1 motifs are coloured dark blue and light blue, respectively. (b) and (c) View of Set1-RRM1 lacking the _3 helix. (b) Same view as in (a). (c) View of the helical side (180° compared to the view in (b)). Side-chains of residues diverging from RNPs consensus sequence are depicted (RNP1, light blue and labelled in bold capitals; RNP2, dark blue and italics). Side-chains of Y271 and F272 are also shown in red. (d)-(f) Comparison of electrostatic surfaces (positive blue and negative red) of Set1-RRM1 and Set1-RRM2 calculated using GROMACS.46 The orientation is the same as in (a); (d) views of Set1-RRM1; (e) Set1-RRM1 with the _3 helix removed; and (f) Set1-RRM2. (g) and (h) Molecular surface of Set1-RRM1 (orientated as in (a)) colour-coded by sequence conservation among 11 Set1 yeast orthologues: conserved residues in 0-3 (white), 4-6 (yellow), 7-9 (orange) and 10 and 11 (red) sequences. (g) View of Set1-RRM1; (h) Set1-RRM1 with the _3 helix removed.

Function Putative RNA-binding or protein-binding domain
Fold RRM fold
Resolution 3.0
Remarks Phased using SIRAS method
Biological unit Monomeric
PDB code Not yet
Reference Tresaugues L, Dehe PM, Guerois R, Rodriguez-Gil A, Varlet I, Salah P, Pamblanco M, Luciano P, Quevillon-Cheruel S, Sollier J, Leulliot N, Couprie J, Tordera V, Zinn-Justin S, Chavez S, van Tilbeurgh H, Geli V. Structural characterization of Set1 RNA recognition motifs and their role in histone H3 lysine 4 methylation. J Mol Biol. 2006 Jun 23;359(5):1170-81

The yeast Set1 histone H3 lysine 4 (H3K4) methyltransferase contains, in addition to its catalytic SET domain, a conserved RNA recognition motif (RRM1). We present here the crystal structure and the secondary structure assignment in solution of the Set1 RRM1. Although RRM1 has the expected ______ RRM-fold, it lacks the typical RNA-binding features of these modules. RRM1 is not able to bind RNA by itself in vitro, but a construct combining RRM1 with a newly identified downstream RRM2 specifically binds RNA. In vivo, H3K4 methylation is not affected by a point mutation in RRM2 that preserves Set1 stability but affects RNA binding in vitro. In contrast mutating RRM1 destabilizes Set1 and leads to an increase of dimethylation of H3K4 at the 5_-coding region of active genes at the expense of trimethylation, whereas both, dimethylation decreases at the 3_-coding region. Taken together, our results suggest that Set1 RRMs bind RNA, but Set1 RNA-binding activity is not linked to H3K4 methylation.